Ingeborg L. Ward - US grants

The objective of this research program is to study the hormonal mechanism(s) acting during prenatal life to determine sexual behavior differentiation. Normal and prenatally stressed rats and guinea pigs will be utilized. We previously had found that exposure to environmental stressors during prenatal life feminizes and demasculinizes sexual behavior in male rats. The complex of changes characteristic of such animals has been termed the prenatal stress syndrome. The etiology of the syndrome appears to be a deficiency in testicular testosterone release on day 18 of gestation. Our research has shown that in normal male fetusus, maximal testosterone titers occur on day 18 of pregnancy. The proposed research will compare fetal plasma LH, pituitary LH and brain LHRH levels as well as the aromatization capacity of specific brain areas during prenatal development with the pattern of plasma testosterone release previously shown to characterize normal and stressed fetuses. The degree to which high testosterone titers on day 18 of gestation are critical to the development of normal male behavior potentials will be probed further by androgenizing females and stressing males during a variety of stages in perinatal life. A more detailed appraisal of the extent to which sexual behavior potentials are altered in prenatally stressed males will be made through adult androgen treatment, exposure to stress in adulthood, or injections of low doses of estradiol. The possible interaction of prenatal stress with prepuberal socializing experiences will be assessed and we plan to test the generality of this syndrome in species other than the rat. Finally, the effects of prenatal stress on the development of reproductive potentials in females will be reevaluated.

Male offspring of mothers stressed during pregnancy show feminized and demasculinized patterns of sexual behavior in adulthood. This so called Prenatal Stress Syndrome has been demonstrated in rats and mice, and may provide insight into intersexed behaviors shown by humans. The several objectives of the present research program include characterizing more completely in prenatally stressed male rats various sexual (e.g. ejaculation, lordosis) and nonsexual (e.g. adolescent play) behaviors known to be organized by exposure to androgens during perinatal life. Secondly, two aspects of the potential mechanism(s) mediating this syndrome will be investigated. The first will utilize radioimmunoassay to determine whether stressed males fail to experience the surge in plasma testosterone during the first hours of birth known to occur in controls. If they do not, critical neonatal factors will have to be considered as playing a causal role in this syndrome which currently is believed to result entirely from an abnormal hormonal milieu during fetal life. The possible involvement of endogenous opiates in the mediation of the Prenatal Stress Syndrome will be assessed by injecting stressed and control mothers with the opiate receptor blocker maltrexone. If stress-induced opiate release is involved then the abnormal adult behavioral and fetal testicular enzyme pattern(s) characteristic of prenatally stressed males should be prevented by pretreating mothers with naltrexone before administering gestational stress. An additional series of studies will investigate the extent to which prepuberal social factors interact with prenatal stress to determine adult sexual behavior potentials and will probe possible physiological mechanisms by which this interaction might be achieved. Finally, an attempt will be made to extend the Prenatal Stress Syndrome to the guinea pig, a laboratory species in which, like man but unlike the rat, sexual differentiation is completed during fetal ontogeny.

Male offspring of mothers stressed during pregnancy show feminized and demasculinized patterns of sexual behavior in adulthood. This so called Prenatal Stress Syndrome has been demonstrated in rats and mice, and may provide insight into intersexed behaviors shown by humans. The several objectives of the present research program include characterizing more completely in prenatally stressed male rats various sexual (e.g. ejaculation, lordosis) and nonsexual (e.g. adolescent play) behaviors known to be organized by exposure to androgens during perinatal life. Secondly, two aspects of the potential mechanism(s) mediating this syndrome will be investigated. The first will utilize radioimmunoassay to determine whether stressed males fail to experience the surge in plasma testosterone during the first hours of birth known to occur in controls. If they do not, critical neonatal factors will have to be considered as playing a causal role in this syndrome which currently is believed to result entirely from an abnormal hormonal milieu during fetal life. The possible involvement of endogenous opiates in the mediation of the Prenatal Stress Syndrome will be assessed by injecting stressed and control mothers with the opiate receptor blocker naltrexone. If stress-induced opiate release is involved then the abnormal adult behavioral and fetal testicular enzyme pattern(s) characteristic of prenatally stressed males should be prevented by pretreating mothers with naltrexone before administering gestational stress. An additional series of studies will investigate the extent to which prepuberal social factors interact with prenatal stress to determine adult sexual behavior potentials and will probe possible physiological mechanisms by which this interaction might be achieved. Finally, an attempt will be made to extend the Prenatal Stress Syndrome to the guinea pig, a laboratory species in which, like man but unlike the rat, sexual differentiation is completed during fetal ontogeny.